One of the problems in the field of chemotherapy is that there is not a clear understanding of the differences between normal and neoplastic cells; consequently, it has not been possible to design chemical compounds which are specific for the cancer cell. In order to gain a more complete understanding of the nature of the cancer cell, it is necessary to learn more about the difference between normal and neoplastic growth in terms of some of the specific enzymes involved in the metabolism of these cells. Ornithine transcarbamylase is an example of an enzyme in which dramatic differences exist between normal liver cells and rapidly growing hepatomas. Delta-N-(phosphonacetyl)-l-ornithine (PAO) has been recently synthesized as an inhibitor of ornithine transcarbamylase. This compound not only inhibits this enzyme but also is a potent inhibitor of growth of mammalian cells in culture such as 3T3, mouse sarcoma (S-180), and Chang liver cells. Thus, PAO and similar compounds may be important chemotherapeutic agents in the treatment of cancer. The major pathway of ammonia detoxification in the human is the urea cycle which is located in the liver. Deficiencies of enzyme activities of these urea cycle enzymes result in hyperammonemia, vomiting, muscular rigidity, intolerance to protein ingestion, and mental deficiency. Congenital hyperammonemia Type II is an ornithine transcarbamylase deficiency and in many of these patients, metabolites of the pyrimidine pathway are greatly increased in urine, especially orotic acid. Ornithine transcarbamylase of E. coli has recently been shown to be activated by orotate as well as other intermediates of pyrimidine biosynthesis. Thus, it appears that there is an important metabolic regulatory link between the intermediates of pyrimidine biosynthesis and the urea cycle.